The present invention relates to analytical chemistry and, more particularly, to ion sources such as those used in chromatograph-spectrometer interfaces. A major objective of the present invention is to provide for alternative thermospray ionization, chemical ionization, and electron impact ionization modes in a single ion source without requiring time-consuming source exchanges.
Analytical chemistry has greatly advanced our ability to understand and protect life by characterizing its constituents and the disease-causing entities that threaten it. These ends have been facilitated by combining chromatographic techniques, which permit the separation of analyte components, and mass spectrometry, which aids in the identification and quantification of components so separated.
Mass spectrometry involves the separation of ions according to their mass-to-charge ratios by a mass filter. A suitable detector, such as a Faraday collector or an electron multiplier, is used to quantify incident ions of the mass-to-charge ratio selected by the mass filter. Generally, the analyte output from a chromatography system is not in the ionized vapor form required for the mass filter. Therefore, the interface between a chromatography system and a mass spectrometer generally includes an ion source which ionizes analyte-bearing gas or fluid output from the chromatography system before the analyte is introduced into the mass spectrometer filter.
Electron impact ionization, chemical ionization, and thermospray ionization are three well-established approaches used in ion sources for chromatograph/spectrometer interfaces. Each approach has its own set of hardware requirements and conditions. The different approaches vary in effectiveness depending on the analyte to be analyzed.
In a typical electron impact ionization source, analyte molecules are introduced in gaseous form into an ionization chamber. A resistive filament disposed near the point of analyte introduction generates high-energy free electrons which bombard the analyte gas molecules. The electrons can be captured by the gaseous analyte or can cause bound electrons to break loose from the analyte molecules, imparting a charge in either case. The pressure within the ionization chamber is kept very low (around 10.sup.-6 to 10.sup.-4 torr) to minimize neutralizing, or de-ionizing, collisions between the ions and other molecules or the apparatus walls. Ions can proceed down a path toward a mass filter or analyzer. The ions can be confined and focused by electromagnetic or electrostatic fields along the ion path through the mass filter or analyzer to the detector.
Chemical ionization as applied to a gaseous analyte is similar to electron impact ionization in that a filament is typically used to generate free electrons that produce ions. However, the primary mechanism by which the molecules of interest are ionized is not direct bombardment. Instead, an intermediary reagent gas is introduced into the chamber. The reagent gas is ionized by the electron bombardment. The analyte gas is then introduced, and is ionized through a chemical reaction with the reagent gaseous ions. Since chemical ionization relies on intermolecular activity for ionization, a sufficiently high density of molecules within the chamber is required to ensure that the desired molecular collisions occur. Therefore, the pressure required for chemical ionization is much greater than that used in electron impact approaches, although generally less than that used in thermospray ionization.
Electron impact and chemical ionization approaches are best suited for gaseous analytes. Such analytes can be provided by gas chromatography systems or by thermally vaporizing the outputs from liquid chromatography systems. However, some molecular products from liquid chromatography disassociate or otherwise fail to remain intact upon vaporization. Accordingly, thermospray ionization permits ionization of an analyte-bearing fluid without requiring thermal vaporization of the analyte.
In a typical thermospray set-up, analyte-bearing liquid eluting from a liquid chromatograph is heated as it flows through a capillary inlet tube into an ionization chamber. The heat vaporizes some but not all of the liquid, primarily carrier fluid or solvent. The vapor forces the analyte into the ionization chamber in the form of a heated spray of droplets of vapor. Evaporation causes spray droplets to shrink.
Uneven distributions of charge result in net charges on some fragment droplets. As these fragment droplets continue to shrink, the net charge can bind to an analyte molecule of interest. The charged molecule can be ejected from the fragment droplet once electric repulsion exceeds the surface tension forces of the droplet. This process is referred to as "ion evaporation". Typically, the ionization chamber for a thermospray apparatus has an ion exit with an axis orthogonal to the axis of the inlet. Pressures within the ionization chamber are relatively high since liquid and vapor are being introduced.
In addition to the ion evaporation mode just described, the thermospray approach admits of a chemical ionization mode. In this mode, a filament is used to ionize evaporated solvent, which is believed to ionize the analyte through a chemical reactions. The filament is placed nearer to the ionization chamber inlet than to the outlet to maximize the number of carrier and solvent molecules available as chemical ionization agents.
Since different approaches are required to ionize different analyte types before their introduction to an ion analyzer, such as a mass spectrometer, it would be advantageous to employ a single ion source which could implement all three ionization approaches described above. Dismantling and modifying ion sources can consume many hours and can significantly reduce analysis throughput and increase analysis costs. Furthermore, subsequent analyses are delayed so that short-lived analytes can be lost before they can analyzed.
Single ion sources have been commercialized which ionize liquid analytes using the thermospray approach in both ion evaporation and chemical ionization modes. In addition, single ion sources are available which combine electron impact and chemical ionization approaches to ionizing gaseous analytes. Heretofore, no single ion source has provided for ionization of both liquid and gaseous analytes. For example, if a user wishes to ionize analytes by thermospray and electron impact, the ion source must be exchanged.
What is needed is a single-chamber ion source that can ionize both liquid and gaseous analytes. More specifically, a multimode source is desired which provides for thermospray, chemical, and electron impact ionization so that the downtime required when switching ion sources can be avoided.